We propose to add the measurement of muscle mass to an already funded program project grant. Rapid declines in physical functioning often occur after the diagnosis of cancer, especially among older cancer survivors; however, a handful of diet and exercise interventions have been found to ameliorate these losses. The contribution of muscle mass and changes in muscle mass in older men and women, particularly those who have survived cancer is not well characterized, partly due to the inability to directly and accurately quantify skeletal muscle mass and reliance on assessments of lean mass as a surrogate. The Adapting MultiPLe behavior Interventions that eFfectively Improve (AMPLIFI) Cancer Survivor Health (1P01CA22997) is aimed at testing three distinct lifestyle interventions among 652 older, inactive, overweight or obese cancer survivors, a large proportion of whom will be minority and rural. The interventions include: 1) a 6-month dietary intervention aimed at improving diet quality and weight loss, as well as preserving lean body mass; 2) a 6-month intervention that is aimed at promoting aerobic physical activity; and 3) a 12-month diet and exercise intervention that combines both diet and exercise simultaneously (and effects will be evaluated against the combination of interventions 1 and 2 in sequence). Visiting nurses will assess physical function and perform phlebotomy at home health assessments scheduled at baseline and every six months; participants also will complete surveys that assess diet, physical activity and overall quality of life. We propose to measure the effects of these interventions on muscle mass using the novel D3-creatine (D3Cr) dilution method. We have demonstrated that this non- invasive method can be implemented in a large cohort study (MrOS) and that D3Cr muscle mass is strongly associated with functional capacity and risk of disability and that age- associated decreases in muscle mass are associated with slower gait speed and decreased strength. These associations were not observed using DXA derived lean mass. Subjects will ingest a 60 mg capsule of D3Cr and produce a fasting urine sample 48 ? 96 hours later for the assessment of D3-Creatinine enrichment to determine creatine pool size and, because 98% of total body creatine is found in muscle, muscle mass. For the first time, the relationship between changes in muscle mass resulting from exercise and weight loss and functional capacity and physical activity will be assessed in this at-risk population of older cancer survivors.